Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS (Combi-LLT ACS)

Samara Regional Cardiology Dispensary

Status: Enrolling

Conditions: Dyslipidemias

Treatments: Combination Product: Combined Lipid-lowering Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05624658

SamaraRCD-1

Details and patient eligibility

About

The study is prospective, open-label, randomized, single-center study involving patients admitted on an emergency basis with an acute coronary syndrome (ACS) clinic who underwent PCI of an infarct-related artery (IRA) and had intermediate coronary artery lesions (50-70% stenosis diameter) and elevated LDL-C ( > 1.4 mmol/l) despite statin therapy at the highest dosage. Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day.

Full description

The study will enroll 120 patients with ACS admitted on an emergency basis to the Hospital. All patients will undergo PCI of the infarct-related artery (IRA), as well as intracoronary imaging with OCT of one or two non-IRA. During hospitalization, patients will receive standard therapy of ACS according to clinical recommendations, while Atorvastatin will initially be prescribed at a maximum dosage of 80 mg / day. Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day.

Also, on the 2nd visit, patients will undergo coronary artery computed tomography (CCTA): assessment of the CAVI index and a laboratory tests (blood count, lipid profile, ALAT, ASAT, Troponin I, Galectin -3, MMP -9, TIMP -1, high-sensitivity CRP, NGAL ). Every 3 months a visit is planned according to the schedule to monitor the effectiveness (blood count, ALAT, ASAT, lipid profile).

Follow up duration will be 52 weeks, according to the schedule of visits. At the final visit, patients will undergo CCTA, CAVI index and laboratory tests (blood count, lipid profile, ALAT, ASAT, Troponin I, Galectin -3, MMP -9, TIMP -1, high-sensitivity CRP, NGAL).

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• gender (any);
• age 18-75 years;
• admission < 24 hours after pain onset
• acute coronary syndrome with at least one coronary artery stenosis requiring PCI;
• one or two non-IRA (coronary artery lumen diameter according to CAG >20% and <50% and no need for revascularization within the next 6 months according to the investigator)
• not taking statins for at least 3 (6) months or not achieving the target level of LDL-C at admission
• failure to achieve the target level of LDL-C ≥1.4 mmol/l on the second visit;
• signed informed consent

Exclusion criteria

• previous MI
• history of revascularization (PCI/CABG)
• presence of non-IRA stenoses ≥50%.
• multivessel lesion, including significant stenosis of the LM
• EF < 40%,
• Killip III-IV.
• NYHA III-IV
• significant calcification or tortuosity of the coronary arteries, limiting OCT
• intolerance to statins, aspirin, P2Y12 inhibitors
• patients who have previously received PCSK9 inhibitors and/or Ezetimib
• treatment with systemic steroids or systemic cyclosporine within the last 3 months
• collagenoses and inflammatory diseases,
• oncological diseases within the last 5 years,
• scheduled surgery within 3 months
• persons suffering from mental disorders
• pregnancy, breastfeeding period

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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200 participants in 2 patient groups

PCSK9 inhibitors in combination Atorvastatin at a dose of 80 mg /Rosuvastatin 40 mg/ day

Active Comparator group

Description:

Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg./ Rosuvastatin 40 mg / day.

Treatment:

Combination Product: Combined Lipid-lowering Therapy

Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/ day.

Active Comparator group

Description:

Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/day.

Treatment:

Combination Product: Combined Lipid-lowering Therapy